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J. Biol. Chem., Vol. 281, Issue 48, 36673-36682, December 1, 2006

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Molecular and Functional Characterization of a Soluble Form of Oncostatin M/Interleukin-31 Shared Receptor^*>

From the Institut National de la Santé et de la Recherche Médicale, U564, F-49033 Angers, France

Activation of the signaling transduction pathways mediated by oncostatin M (OSM) requires the binding of the cytokine to either type I OSM receptor (leukemia inhibitory factor receptor/gp130) or to type II OSM receptor (OSMR/gp130). In the present work we have developed an enzyme-linked immunosorbent assay detecting a soluble form of OSMR (sOSMR) secreted by glioblastoma, hepatoma, and melanoma tumor cell lines. sOSMR was also present in sera of healthy individuals, with increased levels in multiple myeloma. Molecular cloning of a corresponding cDNA was carried out, and it encoded for a 70-kDa protein consisting of a half cytokine binding domain containing the canonical WSXWS motif, an immunoglobulin-like domain, and the first half of a second cytokine binding domain with cysteines in fixed positions. Analysis of the soluble receptor distribution revealed a preferential expression in lung, liver, pancreas, and placenta. sOSMR was able to bind OSM and interleukin-31 when associated to soluble gp130 or soluble interleukin-31R, respectively, and to neutralize both cytokine properties. We have also shown that OSM could positively regulate the synthesis of its own soluble receptor in tumor cells.

Received for publication, July 24, 2006 , and in revised form, August 31, 2006.

^* This study was supported in part by Grant 5176 from the Association pour la Recherche contre le Cancer and by the Post-Genome Program of the Région Pays de la Loire. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S3.

¹ Supported by grants from Angers Agglomeration and the Société Française d'Hématologie.

² To whom correspondence should be addressed: Institut National de la Santé et de la Recherche Médicale, U564, CHU d'Angers, 4 Rue Larrey, F-49033 Angers, France. Tel.: 33-2-41-35-47-31; Fax: 33-2-41-73-16-30; E-mail: gascan{at}univ-angers.fr.

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